Year: 2025
Type: article
Abstract: The growing threat of antibiotic resistance highlights the urgent need for new antimicrobial agents. Nonribosomal peptides (NRPs) are potent antibiotics with complex structures, but generating novel NRP analogues is costly and inefficient. An emerging alternative is using ribosomally synthesized and post-translationally modified peptides (RiPPs), which are gene-encoded, allowing for easier mutagenesis and modification. This study aimed to produce peptides with two key structural elements of many NRP antibiotics: a macrocycle and an N-terminal lipid moiety. The RiPP enzymes SyncM and PirF were employed-SyncM introduced lanthionine or methyllanthionine macrocycles, while PirF incorporated isoprenyl chains to emulate the lipid moieties in NRPs. Both enzymes successfully modified the templates, and their combined use generated lipidated macrocyclic peptides, resembling lipopeptide antibiotics. These findings demonstrate the potential of SyncM and PirF as versatile tools for designing novel gene-encoded NRP mimics, enabling high-throughput screening for new bioactive peptides.
Source: Biomacromolecules
Authors: Yanli Xu, Fleur Ruijne, Manel Garcia Diez, Jorrit Jilles Stada, Oscar P. Kuipers
Institution: University of Groningen
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Award: G5688742902
OpenAlex ID: W4409205564